(CMT 1A) Myelin gene expression altered in cultured Schwann cells by CXCL14

[Guest guest]

Neurobiol Dis. 2008 Dec 10.

The alpha-chemokine CXCL14 is up-regulated in the sciatic nerve of a

mouse model of Charcot-Marie-Tooth disease type 1A and alters myelin

gene expression in cultured Schwann cells.

Barbaria EM, Kohl B, Buhren BA, Hasenpusch-Theil K, Kruse F, Küry P,

i R, Müller HW.

Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-

Heine-University, nstrasse 5, D-40225 Düsseldorf, Germany.

At present the pathogenesis of CMT1A neuropathy, caused by the

overexpression of PMP22, has not yet been entirely understood. The

PMP22-overexpressing C61 mutant mouse is a suitable animal model,

which mimics the human CMT1A disorder. We observed that myelin gene

expression in the sciatic nerve of the C61 mouse was up-regulated at

postnatal day 4 to 7 (P4-P7).

When investigating the morphology of peripheral nerves in C61 and

wildtype mice at early stages of postnatal development,

hypermyelination could be detected in the femoral quadriceps and

sciatic nerve of transgenic animals at postnatal day 7 (P7). In order

to identify genes, other than Pmp22, that are modulated in sciatic

nerve of P7 transgenic mice, we applied microarray technology.

Amongst the regulated genes, the gene encoding the alpha-chemokine

CXCL14 was most prominently up-regulated. We report that Cxcl14 was

expressed exclusively by Schwann cells of the sciatic nerve, as well

as by cultured Schwann cells triggered to differentiate. Furthermore,

in cultured Schwann cells CXCL14 modulated the expression of myelin

genes and altered cell proliferation.

Our findings demonstrate that early overexpression of PMP22, in a

mouse model of CMT1A, results in a strong up-regulation of CXCL14,

which seems to play a novel regulatory role in Schwann cell

differentiation.